Effectiveness and Safety of First-Line Empirical Eradication Therapy with Rebamipide: Results from the European Registry on Helicobacter pylori Management (Hp-EuReg)

Background/Objective: Eradication of Helicobacter pylori typically uses acid-suppressing agents plus antimicrobials, but treatment failure may reach 20–30%. Adjunctive rebamipide has been proposed as a strategy to improve treatment outcomes. This study aimed to assess the effectiveness and safety of first-line empirical therapy when rebamipide was added to eradication regimens. Methods: Treatment-naïve patient data were collected between January 2020 and August 2024 from the European Registry on Helicobacter pylori Management (Hp-EuReg), an international, prospective, multicentre, observational study. Rebamipide-containing regimens were analysed and compared with those without rebamipide. Effectiveness was assessed using a modified intention-to-treat approach. Results: Overall, 4581 patients (mean age 48 ± 15 years, 64% women) from 15 Russian cities were included. From those, 820 patients received eradication therapy with rebamipide and 3761 without rebamipide. Overall effectiveness was significantly higher with rebamipide (731/763, 96%) than without it (2785/3059, 91%) (p = 0.0002). Rebamipide-containing triple therapy consisting of a proton-pump inhibitor (PPI), clarithromycin and amoxicillin was associated with effectiveness above 90%, while rebamipide-containing quadruple therapy consisting of a PPI, clarithromycin, amoxicillin and bismuth yielded a 97% eradication rate, compared with 79% and 95%, respectively, without rebamipide (p < 0.001). Adverse events were significantly more frequent in patients receiving rebamipide-containing regimens (46% vs. 29%, p < 0.0001), though none were serious or caused discontinuation. Compliance was similar in both groups (99% vs. 98.5%; p > 0.05). Conclusions: In this observational registry cohort, first-line empirical triple therapy with amoxicillin–clarithromycin, and quadruple therapy with amoxicillin–clarithromycin–bismuth, both prescribed with rebamipide, were associated with higher eradication rates than regimens without rebamipide.